Abstract: Objective. To compare the main outcomes of radial versus femoral access at long-term follow-up. Background. Little is known about the long-term major cardiovascular events and bleeding complications of patients undergoing percutaneous coronary intervention (PCI) with radial vs femoral approach. Methods. A total of 1107 patients from the CENTURY II trial were included. To minimize baseline differences between radial and femoral groups, we applied propensity-score matching for this comparison. Results. In this multicenter study, the radial approach was used in 73.4% of patients. After propensity-score matching, baseline and procedural characteristics were comparable between both groups. Procedural success was high and similar in radial and femoral approaches (98.2% vs 97.5%; P=.47) while radial access was associated with a shorter hospital stay (1.69 ± 1.92 days vs 2.08 ± 1.98 days; P<.01). The short-term bleeding and vascular complication rates were significantly lower in the radial group (1.7% vs 6.2% [P<.001 in-hospital] and 2.7% vs 9.6% [P<.001 at 1-month follow-up]). At 3-year follow-up, radial access was associated with lower rates of all-cause mortality (3.9 vs 6.9%; P=.04) and cardiovascular death (2.1 vs 4.9%; P=.02). The composite of all-cause mortality, myocardial infarction, and revascularization showed no differences between groups (18.2 vs 21.1%; P=.29). Conclusions. Compared to the femoral approach, the radial approach is associated with significantly lower long-term all-cause mortality rate as well as lower in-hospital and short-term bleeding rates. These results suggest additional long-term benefits of radial access for PCI, but should be interpreted within the context of the current study and further verified in future studies.
J INVASIVE CARDIOL 2018;30(7):262-268.
Key words: radial vs femoral, access site
In the last decades, the radial approach has emerged as the preferred vascular access for coronary angiography. Since its introduction in 1989,1 the percentage of procedures performed by radial approach has experienced a continuous increase, but there is a significant variability in radial use between different centers and countries. Radial vascular access has some well-known advantages over the femoral approach, including effective hemostasis due to the easy compressibility of the radial artery, reduction of vascular complications, and immediate ambulation after the examination. These features have a positive impact on the reduction of hospital stay and hospitalization costs.2 Some studies also showed better results in quality of life questionnaires in patients undergoing procedures by radial approach.3 Nevertheless, this vascular access requires a longer learning curve than the femoral approach, has a higher crossover rate of the access site, and is not always feasible because repeated radial procedures increase the risk of failure. In a study by Abdelaal et al, the success rate was 93% for a second radial attempt, 81% for a third attempt, and declined to 60% for ≥8 procedures.4
Femoral access also has several advantages, mainly for the operator, as it reduces radiation exposure,5 allows the use of larger catheters in complex percutaneous coronary interventions (PCI), and may enable better control of the catheter. Indeed, catheter torquability is not hindered by severe tortuosity of the subclavian artery that may be present in some cases performed by radial approach. On the other hand, the femoral approach is associated with higher bleeding and vascular complication rates.
The radial approach for PCI has been validated in numerous trials and meta-analyses showing a reduction in bleeding complications.6 In patients presenting with an acute coronary syndrome (ACS), radial compared to femoral access reduces major bleeding and all-cause mortality.6,7 In ST-segment elevation myocardial infarction (STEMI) patients, the results of the RIFLE-STEACS trial showed that radial approach was associated with significantly lower rates of cardiac mortality and bleeding, as well as shorter hospital stay.8 However, the results of these studies must be interpreted with caution due to several limitations including the strong modulating effect of operator/center experience on the relative efficacy of radial approach.9
The follow-up of the main studies comparing radial vs femoral access was limited to 30 days. It is not known whether the in-hospital and short-term advantages shown by the radial approach in these trials have an impact on outcomes at longer-term follow-up. Thus, the aim of the present study was to compare the main outcomes of radial vs femoral access at 3-year follow-up in a large cohort of patients undergoing PCI.
Study design. From February 2012 to January 2013, a total of 1123 patients were enrolled in the CENTURY II (Clinical Evaluation of New TerUmo dRug-eluting coronarY stent system in the treatment of patients with coronary artery disease) trial.10 This trial was a single-blind, randomized, multicenter study comparing the sirolimus-eluting bioresorbable-polymer Ultimaster stent (Terumo Corporation) to the everolimus-eluting durable polymer Xience stent (Abbott Vascular). A total of 58 centers from Europe, Japan, and Korea enrolled patients meeting the study inclusion criteria. The study design incorporated the general requirements for drug-eluting stent (DES) implantation in Europe and in Japan. Main exclusion criteria for participation in this study were: target-lesion vessel diameter <2.5 mm or >4.0 mm (>3.5 mm in Japan); life expectancy <1 year; allergy or intolerance to sirolimus, everolimus, or dual-antiplatelet treatment; left ventricular ejection fraction <25%; coagulopathy; cardiogenic shock; renal failure requiring dialysis; or inability to provide written informed consent.10 In the Japanese cohort, additional exclusion criteria were added to the study protocol in order to match approved indications for DES and regulatory requirements in Japan.10
All patients included in this study underwent PCI following the standard procedure at each participating center. The choice of the arterial access, as well as other procedural variables like predilation, postdilation, or intracoronary imaging use, were left at the discretion of the operator. A quality-of-life analysis based on the EQ-5D questionnaire was performed in 228 patients at baseline and at 9-month follow-up.
Follow-up was scheduled at 30 days, 4 months, 9 months, 1 year, 2 years, and 3 years. The 3-year follow-up rate was 96.4%.
Endpoints and definitions. The study objective was to compare the main short-term and long-term outcomes of patients included in the CENTURY II trial who underwent PCI by radial vs femoral approach. The primary endpoint of our study was all-cause mortality at 3 years. The secondary endpoints included cardiovascular mortality, myocardial infarction, all revascularization, and the composite of all-cause mortality, myocardial infarction, and revascularization. The main safety endpoint was bleeding and vascular complication rate at 30 days after the index procedure. Bleeding was defined according to the Bleeding Academic Research Consortium (BARC) criteria.11
Statistical analysis. Continuous variables are presented as mean ± standard deviation and were compared using the 2-tailed Student’s t-test. Categorical variables were compared using the Chi-square test or Fisher’s exact test, as appropriate. A P-value <.05 was considered statistically significant. Because the patients were not randomly assigned to undergo PCI by radial or femoral approach, a propensity-score analysis was performed in order to reduce the effect of baseline differences between groups. The variables used in propensity matching included age, body mass index, gender, hypertension, diabetes, dyslipidemia, current smoker, renal disease, multivessel disease, multivessel treatment, previous myocardial infarction, previous PCI, previous coronary artery bypass graft (CABG) surgery, stroke, STEMI, predilation, postdilation, number of stents implanted, and left main or proximal left anterior descending (LAD) artery disease. We calculated propensity score for weighting using inverse probability of treatment weighting, and then we normalized weights according to the sample size of each group. Weights are expressed as non-integer numbers; when performing weighting, binary variables can become non-integers. The cumulative incidence of clinical events at follow-up was assessed using the Kaplan-Meier method. All data were processed using SAS software, version 9.1 (SAS Institute, Inc).
After excluding 16 patients who underwent procedure via brachial approach, 1107 patients from 58 participating centers in 13 countries in Europe, Korea, and Japan were included in this radial vs femoral substudy. Baseline characteristics of both groups are listed in Supplemental Table S1 (parts 1 and 2). Radial access was used in 73.4% of the patients included in the CENTURY II study, while 90.7% underwent PCI by radial approach in the Japanese cohort. Female patients of an older age and with a history of previous myocardial infarction or CABG were more likely to undergo a femoral approach. The femoral approach was the preferred vascular access for STEMI as well as for complex PCI cases, such as those with high SYNTAX score, multivessel disease, left main, or proximal LAD disease. Due to higher procedural complexity, the coronary lesions treated via femoral approach were more frequently predilated and postdilated and needed a greater number of stents than lesions treated via radial approach. The unadjusted rate of all-cause mortality at 3-year follow-up was higher in the femoral group (3.4% vs 7.5%; P<.01), as was the cardiovascular mortality rate (1.7% vs 5.4%; P<.001). The femoral approach was associated with a significant increase in the rate of bleeding events (2.8% vs 10.5%; P<.001) at 1-month and 3-year follow-up (14% vs 19.7%; P=.02).
Because the patients included in this study were not randomly assigned to undergo procedures by radial or femoral approach, a propensity-score matching was performed in order to adjust for differences between the main baseline and procedural characteristics. After propensity-score matching, 800 out of 813 patients in the radial group and 265 out of 294 patients in the femoral group were included in the final analysis. The main characteristics of the patients included in the study after propensity-score matching are listed in Table 1 (parts 1 and 2). The mean patient age was 65 years and 81% were male. In the matched cohorts, the main baseline and procedural characteristics, including diabetes, renal disease, left ventricular ejection fraction, previous myocardial infarction, and CRUSADE bleeding score, were comparable between groups. Radial PCI was performed more frequently in patients with unstable angina (13.4 vs 7.1%; P<.01) but no differences were found in the percentages of ACS or STEMI in radial vs femoral groups. The complexity of coronary lesions undergoing PCI (left main coronary artery, proximal LAD, chronic total occlusions, bifurcations, and number of vessels treated) was also similar in the two groups. Complete revascularization of all significant coronary stenosis was achieved in 70.7% of patients. Procedural success rates were high and similar in both groups (98.2% vs 97.5%; P=.47). The radial approach was associated with a shorter hospital stay after the index procedure (1.69 ± 1.92 days vs 2.08 ± 1.98 days; P<.01). The short-term bleeding and vascular complication rates were significantly lower in the radial group (1.7% vs 6.2% in-hospital and 2.7% vs 9.6% at 1-month follow-up; P<.001 for both). Table 2 shows clinical and safety endpoints at 30-day follow-up. Total bleeding and vascular complication rates at 3-year follow-up were 14.3% in the radial group and 18.3% in the femoral group (P=.12) (Table 3 and Figure 1).
At 3-year follow-up, there were 49 deaths (4.6%). After propensity-score matching, radial access was associated with a lower all-cause mortality rate (3.9% vs 6.9%; P=.04) and a lower cardiovascular death rate (2.1% vs 4.9%; P=.02) at 3-year follow-up (Table 3 and Figure 2). The composite of all-cause mortality, myocardial infarction, and revascularization showed no differences between radial and femoral groups (18.2 vs 21.1%; P=.29).
A quality-of-life analysis based on the EQ-5D questionnaire was performed at baseline and at 9-month follow-up. No statistical differences in the EQ calculated index score were found between patients who underwent radial vs femoral procedure at baseline (0.81 ± 0.18 vs 0.80 ± 0.21; P=.64) or 9 months after PCI (0.86 ± 0.18 vs 0.89 ± 0.13; P=.20).
In the present study, performed at 58 centers in 13 countries in Europe, Korea, and Japan, radial access was the preferred approach in nearly three-quarters of PCIs. Indeed, radial approach has become the predominant access site for coronary angiography and PCI in many countries, although significant differences in its adoption have been reported worldwide.12 The largest PCI registry in the United States, including more than 1400 participating centers, showed that only 6.5% of operators performed >10% of their PCIs by radial approach in 2009. Despite the growing number of radial PCIs in recent years, femoral access is still the preferred approach for PCI in the United States.13 Helfrich et al conducted a national survey to study the perception of the radial approach among American interventional cardiologists. The results of this study showed that even interventional cardiologists from sites performing few radial procedures recognized the superiority of the radial approach for improved patient comfort and safety. A perceived long learning curve and concerns about radiation exposure were identified as the most important barriers to the implementation of radial use in centers across the United States.12,14
In the present study, radial access showed lower rates of cardiovascular and all-cause mortality at 3-year follow-up compared to the femoral approach. Unlike prior large studies comparing femoral and radial approaches for PCI, our study shows differences in mortality among a lower-risk population since ACS represented only 36.5% of PCI indications in our cohort. Furthermore, little is known about the long-term outcomes of PCI performed by radial vs femoral approach, as most of the previous large studies provided only short-term follow-up data. Our main results are consistent with numerous registries, studies, and meta-analyses showing that the radial approach is associated with a reduced rate of access-site related bleeding complications and mortality.6,7,12,15 Based on these results, the 2014 European guidelines on myocardial revascularization stated that radial access should be preferred over femoral access if performed by an experienced radial operator (class of recommendation IIa, level of evidence A).16 Nevertheless, the results of the RIVAL randomized trial failed to show significant differences in major cardiovascular events or even in major bleeding;17 hence, the controversy between radial and femoral approach is still ongoing. When analyzing the inclusion criteria, we found that an operator experience of only 50 radial catheterizations was required for participation in RIVAL. The reduced radial training, without a specific requirement for radial PCI, has probably impacted the results of the radial approach in this study and was an important study limitation.7 Moreover, the results of RIVAL show that in centers undertaking a high number of radial procedures and with lower crossover rates, the radial approach seemed to be associated with fewer bleeding complications than femoral approach. After the publication of the RIVAL trial, and with full awareness of some of its limitations, two other large randomized studies (RIFLE-STEACS and MATRIX)7,8 were conducted. Both confirmed a significant reduction of mortality in ACS patients undergoing invasive management by radial access. This approach seems to be even more beneficial in high-risk populations, such as STEMI patients, who receive potent antithrombotic therapy and have increased bleeding risk.18,19 As a result, current European STEMI guidelines recommend radial access for primary PCI when performed by an experienced radial operator.20 A study from a high-volume radial center showed that primary PCI via the radial artery was feasible in 95% of patients, with a crossover rate to the femoral approach of only 2.2%. Of note, failure to perform a radial access in STEMI patients included in this study was associated with increased mortality and higher incidence of bleeding complications.21
In our study, the femoral approach showed higher rates of bleeding and vascular complications at 1-month follow-up (Figure 1). Bleeding events have a direct impact on patient prognosis, as major periprocedural bleeding is independently associated with a three-fold increase in mortality.22 In a large study of more than 3 million PCIs, major bleeding was associated with a significantly increased in-hospital mortality rate, with 12.1% of all in-hospital deaths after PCI related to bleeding complications.23 A large Canadian PCI registry showed that transradial access reduces the transfusion rate and is associated with a reduction in 30-day and 1-year mortality rates.24 Although the reduction in bleeding associated with the radial approach contributes to decrease mortality, other studies have suggested that the reduction in mortality cannot be explained by reducing bleeding events alone.12,24,25
Transulnar access could also be considered as an alternative approach in cases of radial access failure,26,27 although much less is known about outcomes using this alternative access route. However, the access site should be chosen based on the clinical situation and operator experience.
The results reported in our study are consistent with previous randomized trials and add long-term data suggesting a superiority of radial approach for PCI. Further long-term studies are needed to provide additional evidence to recommend radial access as the primary approach for PCI. In complex PCI cases, use of the radial approach will probably continue to increase in the next years, as it is favored by a growing experience of interventional cardiologists, and some technology evolutions like dedicated 7 Fr Glidesheath slender28 and sheathless catheters may even allow use of an 8 Fr catheter by radial approach.29
Study limitations. Our results should be interpreted in the context of the study design and have some limitations. First, the choice of the vascular access site was not randomized, and despite adjusting variables using propensity-score matching, additional confounders cannot be completely excluded. Hence, our results showing higher all-cause mortality at 3-year follow-up in the femoral group could be due to other variables not included in the present study. Despite an equivalent Charlson comorbidity index and similar baseline characteristics, it is possible that frail patients underwent femoral PCI more frequently. As our study was performed mainly in centers where radial access is the preferred approach, the results could also indicate that the inability to perform a PCI by radial approach at the participating centers probably identifies a higher-risk population with worse long-term prognosis. Second, our study does not provide the crossover rates from radial to femoral access or the use of vascular closing devices. Third, no data were available regarding radiation exposure for either approach.
Compared to the femoral approach, the radial approach is associated with significantly lower long-term all-cause mortality rate as well as lower in-hospital and short-term bleeding rates. These results suggest additional long-term benefits of radial access for PCI; however, they should be interpreted within the context of the current study and further verified in future studies.
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From the 1Hôpital Rangueil, CHU Toulouse, France; 2Centro Cardiologico Monzino, University of Milan, Italy; 3Kanto Rosai Hospital, Japan; 4Hopital Privé Jacques Cartier (ICPS), Massy, France; 5Kyoto University Graduate School of Medicine, Japan; 6Hospital de la Santa Creu i Sant Pau, Spain; 7Hôpital Cochin, Paris, France; 8CHU Charleroi, Belgium; 9Kurashiki Central Hospital, Japan; 10Tokai University Hospital, Japan; 11Sakakibara Heart Institute, Japan; 12Sakurabashi Watanabe Hospital, Japan; 13Kyoto Katsura Hospital, Japan; 14Shonan Kamakura General Hospital, Japan; 15Cardiovascular Research Center, OLV Hospital, Aalst, Belgium; and 16Lambe Institute for Translational Medicine and Curam, National University of Ireland, Galway, Ireland.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Ikari reports patent income for the Ikari curve device. Dr Varenne reports personal fees from Boston Scientific, Abbott Vascular, and Astra Zeneca. Dr Wijns reports grants from MiCell Technologies, MicroPort, Abbott-St. Jude, and Terumo; shareholder in Argonauts and Genae; member of the advisory board of MicroPort. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted January 17, 2018, final version accepted March 26, 2018.
Address for correspondence: Francisco Campelo-Parada, MD, Hôpital Rangueil, CHU Toulouse, 1 Avenue Jean Poulhès, 31059 Toulouse, France. Email: firstname.lastname@example.org